Effect of pravastatin on nephroprotection in deoxycorticosterone acetate-salt hypertensive rats

Chih Sen Kang, Nen Chung Chang, Shen Tien Chang, Chih Chan Lin, Tsung-Ming Lee

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Objective Endothelin-1 (ET-1) has been implicated in the pathogenesis of renal impairment. The current study was undertaken to assess the effect of pravastatin on the progression of renal impairment in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Methods Four weeks after the start of DOCA-salt treatment and uninephrectomization, male Wistar rats were treated with one of the following therapies for 8 weeks: vehicle; a nonselective endothelin receptor antagonist bosentan; pravastatin; or hydralazine. Results Treatment with bosentan or pravastatin was associated with reductions in blood pressure and renal medullary hydroxyproline content, and improvement in glomerular filtration rate, urinary protein excretion, macrophage infiltration, tubular injury, and vascular injury, but not glomerulosclerosis. The renal medullary ET-1 protein levels and preproET-1 mRNA assessed by western blotting and real-time quantitative reverse transcription-PCR were significantly decreased (both P<0.001) in the pravastatintreated rats compared with vehicle, which was also confirmed by immunohistochemical analysis. However, there were no significant differences of ET-1 levels in the renal cortex among the DOCA-salt groups. The nephroprotective effects of pravastatin were not associated with its antihypertensive action because hydralazine despite reducing blood pressure failed to improve renal function and disorder. Conclusion These results suggest a crucial role of renal endothelin system in the pathogenesis of renal functional and structural alterations in the DOCA-salt hypertensive rats. Pravastatin administration ameliorates the impairment of renal function and structures by attenuating medullary ET-1 expression, independent of systemic blood pressure.

Original languageEnglish
Pages (from-to)2232-2243
Number of pages12
JournalJournal of Hypertension
Volume27
Issue number11
DOIs
Publication statusPublished - Nov 2009

Fingerprint

Pravastatin
Desoxycorticosterone
Acetates
Salts
Kidney
Endothelin-1
Hydralazine
Blood Pressure
Vascular System Injuries
Endothelins
Hydroxyproline
Glomerular Filtration Rate
Antihypertensive Agents
Reverse Transcription
Wistar Rats
Proteins
Western Blotting
Macrophages
Polymerase Chain Reaction
Messenger RNA

Keywords

  • Deoxycorticosterone Acetate-Salt rats
  • Endothelin-1
  • Immunohistochernistry
  • Pravastatin

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Effect of pravastatin on nephroprotection in deoxycorticosterone acetate-salt hypertensive rats. / Kang, Chih Sen; Chang, Nen Chung; Chang, Shen Tien; Lin, Chih Chan; Lee, Tsung-Ming.

In: Journal of Hypertension, Vol. 27, No. 11, 11.2009, p. 2232-2243.

Research output: Contribution to journalArticle

Kang, Chih Sen ; Chang, Nen Chung ; Chang, Shen Tien ; Lin, Chih Chan ; Lee, Tsung-Ming. / Effect of pravastatin on nephroprotection in deoxycorticosterone acetate-salt hypertensive rats. In: Journal of Hypertension. 2009 ; Vol. 27, No. 11. pp. 2232-2243.
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